Nagareddy Publication Tops Cell Metabolism 10th Anniversary List
Cell Metabolism 10th Anniversary Top 10 Breakthroughs in Immunometabolism.
Now with the University of Kentucky Saha Cardiovascular Research Center, Dr. Prabhakara R. Nagareddy publication is at top of list.
Adipose Tissue Macrophages Promote Myelopoiesis and Monocytosis in Obesity
Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, Dragoljevic D, Hong ES, Abdel-Latif A, Smyth SS, Choi SH7, Korner J, Bornfeldt KE, Fisher EA, Dixit VD, Tall AR5, Goldberg IJ, Murphy AJ.
Summary
Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1β production. IL-1β interacted with the IL-1 receptor on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1β signaling axis could reduce AT inflammation and insulin resistance in obesity.